CONFORMATIONAL PROPERTIES OF TAU-DERIVED PEPTIDE FILAMENTS IN ALZHEIMER’S DISEASE

摘要

We examined hierarchically self-assembled fβ-sheet filaments consisting of a six-residue tau-derived peptide (AcPHF6) using atomistic modeling and molecular dynamics (MD) simulations. First, relative stability was determined among possible association patterns between two β-sheet monolayers. This allowed us to identify the most probable conformations either in bilayers or laterally associated tapes. We further considered assembly into extended bilayers made up of four fβ-sheets, which yielded two most probable patterns. These may serve as building blocks for larger assemblies such as nanotubes or laminated tapes observed in experiments. Our modeling and simulation approaches can thus be applied to various self-assembled fβ- sheet structures and find how intermolecular interactions affect the large-scale organization of the filaments.